EP0284407B1 - Formulations de 3'-azido-3'-déoxythymidine à libération contrôlée - Google Patents
Formulations de 3'-azido-3'-déoxythymidine à libération contrôlée Download PDFInfo
- Publication number
- EP0284407B1 EP0284407B1 EP88302657A EP88302657A EP0284407B1 EP 0284407 B1 EP0284407 B1 EP 0284407B1 EP 88302657 A EP88302657 A EP 88302657A EP 88302657 A EP88302657 A EP 88302657A EP 0284407 B1 EP0284407 B1 EP 0284407B1
- Authority
- EP
- European Patent Office
- Prior art keywords
- pharmaceutical formulations
- coating
- zidovudine
- particles
- spheroid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5015—Organic compounds, e.g. fats, sugars
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5026—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5036—Polysaccharides, e.g. gums, alginate; Cyclodextrin
- A61K9/5042—Cellulose; Cellulose derivatives, e.g. phthalate or acetate succinate esters of hydroxypropyl methylcellulose
- A61K9/5047—Cellulose ethers containing no ester groups, e.g. hydroxypropyl methylcellulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
Definitions
- the present invention relates to controlled release pharmaceutical formulations comprising 3'-azido-3'-deoxythymidine, and their use for the treatment or prophylaxis of certain viral infections more particularly human retroviral infections such as Acquired Immune Deficiency Syndrome (AIDS).
- AIDS Acquired Immune Deficiency Syndrome
- AIDS is an immunosuppressive or immunodestructive disease that predisposes subjects to fatal opportunistic infections. Characteristically, AIDS is associated with a progressive depletion of T-cells, especially the helper-inducer subset bearing the OKT 4 surface marker.
- HIV Human Immunodeficiency Virus
- European Patent Specification 52075 describes a granular delayed-release form of pharmaceutically active substances in which a granulated or crystalline pharmaceutically active substance is coated with a mixture of a polyacrylate and a cellulose either.
- compositions adapted for oral administration in the form of spheroid particles having a diameter of 0.5 to 2 mm and comprising a homogenous mixture of 75-99% w/w of zidovudine together with one or more excipients, such particles each being provided with a controlled release coating comprising a mixture of (a) a non-ionic polymer of at least one monomer selected from alkyl esters of acrylic and methacrylic acids, and (b) ethyl cellulose components (a) and (b) being present in the coating in a weight ration of 1 : 3 to 3 : 1.
- component (a) is preferably a homopolymer of one or more Chalky) esters of acrylic and/or methacrylic acid, eg. methyl or ethyl acrylate.
- Chalky esters of acrylic and/or methacrylic acid
- eg. methyl or ethyl acrylate is a particular example of such polymers.
- Eudragit NE30D@ from Rohm Pharma GmbH (Darmstadt, West Germany).
- Such polymers when used alone, provide a coating which is substantially insoluble in the pH range found in the gastro-intestinal tract but which is permeable to the fluids in the tract to permit some release of drug.
- Component (b) in the above coating is preferably applied to the zidovudine cores in the form of an aqueous dispersion for example using a 30% dispersion commercially available under the trade name AquacoatO from FMC Corporation or a 30% dispersion available under the trade name Surelease from Colorcon Ltd.
- the above coating preferably comprises components (a) and (b) in weight ratio of about 1 : 1.
- the coating advantageously contains a pore-forming agent to provide further control of the release of zidovudine, for example water-soluble materials such as sodium chloride, polyethylene glycols, lactose, sucrose or preferably mannitol.
- a pore-forming agent to provide further control of the release of zidovudine
- water-soluble materials such as sodium chloride, polyethylene glycols, lactose, sucrose or preferably mannitol.
- Such an agent is preferably present in the coating in an amount of 15 to 50% wiw advantageously about 40% w/w.
- the coating may comprise for example 1-10% wlw. preferably 3-8% of said spheroid particles.
- zidovudine and any necessary excipients are mixed with a liquid to form a wet extrudable mass.
- the mass is then extruded and the extrudate transferred to a spheroniser containing a plate which is rotated generally at 150-2000 rpm depending on the diameter of the plate.
- the surface of the plate is usually roughened with a regular pattern or grid.
- the extrudate is initially broken down by the rotary motion of the plate into short sections or pellets.
- the material is sufficiently plastic for these pellets to be spheronised by the frictional forces on the plate which gives a rolling motion and also by the interparticulate friction of the revolving pellets.
- the resulting spheroid particles are removed from the plate and dried before coating.
- the constitution of the extrudate is critical for the formulations of a material that can be processed to form spheroid particles of appropriate size and shape.
- An extrudate having a satisfactory constitution will normally show adequate cohesion and will break up into the required lengths having an essentially smooth surface. If the constitution is incorrect, the extrudate may be too friable or too plastic and will not fragment into short sections having the required length, and thus will not form pellets of essentially uniform diameter.
- extrudates have usually required at least 30% (dry weight) of exipients providing a final maximum concentration of 70% of the drug in the spheroid particles and previous attempts to prepare such particles containing high concentrations of drugs of various types have been largely unsuccessful.
- zidovudine can be successfully combined with extrusion excipients to provide extrudates containing up to 90% or more of drug that still retain workability on spheronisation.
- Spheroids particles having desirable handling characteristics and size distribution and containing high concentrations of zidovudine can thereby be obtained.
- excipient(s) will generally include an extrusion aid, i.e. a material which, when mixed with the desired quantity of zidovudine and an appropriate amount of water or other liquid or solution, provides mixtures that can be extruded and spheronised in conventional manner as described above.
- an extrusion aid i.e. a material which, when mixed with the desired quantity of zidovudine and an appropriate amount of water or other liquid or solution, provides mixtures that can be extruded and spheronised in conventional manner as described above.
- Such a material will generally be present in an amount of 1-25% wlw of the spheroid particles.
- extrusion aids include microcrystalline cellulose described in the U.N. National Formulary, e.g. as sold under the trade nam Avicel®, especially microcrystalline cellulose having an average particle size of 50-100 ⁇ e.g. Avicel PH101®.
- microcrystalline cellulose materials have been found to be particularly advantageous as excipients in the formulations according to the invention in enabling one to prepare by extrusion spherical particles containing high concentrations of drug as referred to above.
- extrusion aids include those described in Microcrystalline Polymer Science by O.A. Battista, McGraw-Hill (1975) such as microcrystalline collagens and amyloses, pregelled starch, and also pharmaceutically acceptable clays such as kaolin, bentonite, or attapulgite.
- the active ingredient may be present for example in concentrations of at least 80% w/w and generally less than 95% w/w.
- binders include low viscosity, high-molecular weight water-soluble polymeric material such as polyvinylpyrrolidone, e.g. povidone as described in U.S. National Formulary especially material available commercially as Kollidon@ K30 or K90, vinylpyrrolidone/vinyl acetate copolymers especially Kollidon VA 640, hydroxypropylmethyl cellulose or sodium carboxymethylcellulose or other cellulose binders.
- Such binders may generally be present in the spherical particles in amounts of up to 20% wlw, e.g. 2-5% w/w.
- excipients which may be present in the particles, include for example bulking agents such as lactose, mannitol or sucrose, e.g. in amounts up to 10% w/w.
- the spheroid particles in the formulations according to the invention advantageously have a diameter of 0.80 to 1.40 mm and are preferably provided with a controlled release coating comprising a non-ionic polymer and ethyl cellulose as described.
- a process forthe preparation of the above- described pharmaceutical formulations which comprises forming an extrudable mass comprising 75 to 99% w/w (dry weight) of zidovudine together with one or more excipients, and a pharmaceutically acceptable liquid, e.g. water, extruding the said mass ; subjecting the extrudate to spheronisation to form spheroid particles having a diameter of 0.5 to 2 mm ; and providing the said particles with a controlled release coating as defined above.
- a pharmaceutically acceptable liquid e.g. water
- the initial step of forming an extrudable mass generally comprises the admixture of the dry ingredients and the pharmaceutically acceptable liquid. If a binder solution is employed, the separate addition of the liquid may not be necessary.
- the extrudable mass will contain 10 to 40% preferably 20 to 35% (based on the total weight of the mass) of water.
- the mass is then passed through an extruder at an appropriate rate, the extrudate emerging from the aperture(s) of the extruder as long spaghetti-like strands, which break up under their own weight into shorter strands and are further reduced in length and subsequently formed into spheroid particles having the desired size in a spheronising apparatus.
- the particles are then removed from the spheronising apparatus, dried and coated.
- coated spheroid particles of the pharmaceutical formulations according to the invention are preferably presented in the form of unit doses for example in tablets or capsules, e.g. gelatin capsules, providing a predetermined specific amount of active ingredient (zidovudine) advantageously 50 to 1000 mg, preferably 100 to 500 mg thereof.
- active ingredient zidovudine
- the controlled release coating of the formulations according to the invention may include other appropriate excipients, eg an anti-agglomerating agent such as magnesium stearate, talc, kaolin or colloidal silica, eg Aerosil® to prevent sticking of the coated cores.
- an anti-agglomerating agent such as magnesium stearate, talc, kaolin or colloidal silica, eg Aerosil® to prevent sticking of the coated cores.
- the coatings may be applied to the discrete units in conventional manner, eg. by suspending the polymer and any other coating components in an appropriate liquid medium such as water, for example forming a dispersion of the polymers which is then applied to the discrete units by spray coating, for example in a fluid bed to form a coating of appropriate thickness.
- an appropriate liquid medium such as water
- spray coating for example in a fluid bed to form a coating of appropriate thickness.
- Other methods of applying the coatings include pan coating etc.
- Zidovudine may be prepared for example as described in the above-mentioned European Patent Specification or by methods known in the art or analogous thereto.
- the formulations according to the invention may be employed for the treatment or prophylaxis of various viral infections particularly human retroviral infections such as HIV infections and related conditions such as AIDS, AIDS-related complex (ARC) and progressive generalised lymphadeopathy (PGL), and AIDS-related neurological conditions such as multiple sclerosis and tropical spastic paraparesis.
- human retroviral infections include Human T-cell Lymphotropic virus (HTLV)-I and IV and HIV-2 infections.
- the invention accordingly provides pharmaceutical formulations according to the invention for use in the treatment or prophylaxis of the above-mentioned human retroviral infections.
- the pharmaceutical formulations are generally administered in a dose in the range of 1.0 to 120 mg per kilogram body weight of the recipient per day, preferably in the range of 1.0 to 100 mg per kilogram body weight per day and most preferably in the range 5 to 40 mg per kilogram body weight per day.
- the desired dose is preferably presented as two, three, or more sub-doses administered at appropriate intervals throughout the day. These sub-doses may be administered in unit dosage form, for example, containing 10 to 1000 mg, and most preferably 100 to 500 mg of active ingredient per unit dosage form.
- the formulations should be desirably administered to achieve peak plasma concentrations of the active compound of from about 1 to about 100 ⁇ M, preferably about 2 to 50 uM, most preferably about 3 to about 30 uM.
- the mannitol was dissolved in the water.
- the Eudragit and Aquacoat were then added with gentle mixing.
- the coating mixture was applied to 100 g of dry cores prepared as described in Example 1 or 2 using a fluidised bed unit equipped for spray coating. A quantity was applied so as to give a 6% coat.
- the coated cores were dried and filled into capsules. Dissolution tests were carried out on the cores in the USP rotating paddle apparatus at 50 rpm with water as the dissolution medium. Samples were analysed by UV spectroscopy and % released versus time values calculated :
- the active ingredient and microcrystalline celulose are mixed.
- the povidone is dissolved in purified water and added to the blend to granulate.
- Marumes are formed by passing the granules through an extruder and a spheronizer. The marumes are dried.
- the mannitol is dissolved in purified water.
- the Eudragit NE30D@ and Aquacoat ECD-30® are added and mixed into the solution.
- the marumes are coated with the suspension, purified talc added to the coated pellets if necessary.
- the coated pellets are filled in hard-gelatin capsules.
- the capsule formulation was prepared as described in Example 4.
Claims (10)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AT88302657T ATE63818T1 (de) | 1987-03-27 | 1988-03-25 | 3'-azido-3'-deoxythymidin-formulierungen mit gesteuerter freigabe. |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB878707421A GB8707421D0 (en) | 1987-03-27 | 1987-03-27 | Pharmaceutical formulations |
GB8707421 | 1987-03-27 |
Publications (3)
Publication Number | Publication Date |
---|---|
EP0284407A2 EP0284407A2 (fr) | 1988-09-28 |
EP0284407A3 EP0284407A3 (en) | 1988-12-14 |
EP0284407B1 true EP0284407B1 (fr) | 1991-05-29 |
Family
ID=10614823
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP88302657A Expired - Lifetime EP0284407B1 (fr) | 1987-03-27 | 1988-03-25 | Formulations de 3'-azido-3'-déoxythymidine à libération contrôlée |
Country Status (17)
Country | Link |
---|---|
US (1) | US4917900A (fr) |
EP (1) | EP0284407B1 (fr) |
JP (1) | JP2719344B2 (fr) |
KR (1) | KR960013434B1 (fr) |
AT (1) | ATE63818T1 (fr) |
AU (1) | AU607474B2 (fr) |
CA (1) | CA1308026C (fr) |
DE (1) | DE3862974D1 (fr) |
DK (1) | DK175348B1 (fr) |
ES (1) | ES2033426T3 (fr) |
GB (1) | GB8707421D0 (fr) |
GR (1) | GR3002030T3 (fr) |
IE (1) | IE60605B1 (fr) |
IL (1) | IL85870A (fr) |
NZ (1) | NZ224026A (fr) |
PT (1) | PT87081B (fr) |
ZA (1) | ZA882168B (fr) |
Families Citing this family (31)
Publication number | Priority date | Publication date | Assignee | Title |
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US5051361A (en) * | 1988-10-19 | 1991-09-24 | Sigma Chemical Company | AZT immunoassays, derivatives, conjugates and antibodies |
US4938966A (en) * | 1988-11-30 | 1990-07-03 | Riker Laboratories, Inc. | Controlled release flecainide acetate formulation |
GB8912420D0 (en) | 1989-05-31 | 1989-07-19 | Schram Cornelius J | Ultrasonic systems |
EP0452862B1 (fr) * | 1990-04-18 | 1995-07-19 | Asahi Kasei Kogyo Kabushiki Kaisha | Noyaux des germes sphériques, granules sphériques et procédé de leur préparation |
US5102668A (en) * | 1990-10-05 | 1992-04-07 | Kingaform Technology, Inc. | Sustained release pharmaceutical preparation using diffusion barriers whose permeabilities change in response to changing pH |
WO1993000351A1 (fr) * | 1991-06-21 | 1993-01-07 | Acic (Canada) Inc. | Nouveaux composes antiviraux et procede de preparation de composes antiviraux |
KR100221695B1 (ko) * | 1991-08-12 | 1999-09-15 | 그린 마틴, 브라이언 쥐 테슬리 | 약학적 구상 제형 |
EP0654038B1 (fr) * | 1992-08-04 | 1999-11-10 | James M. Dunn | Formulations pharmaceutiques a liberation regulee de 3'-azido-3'-desoxythymidine |
FR2698560B1 (fr) * | 1992-11-30 | 1995-02-03 | Virbac Laboratoires | Principes actifs pulvérulents stabilisés, compositions les contenant, leur procédé d'obtention et leurs applications. |
US6245351B1 (en) | 1996-03-07 | 2001-06-12 | Takeda Chemical Industries, Ltd. | Controlled-release composition |
DE19945982A1 (de) * | 1999-09-24 | 2001-03-29 | Knoll Ag | Geschwindigkeitsbestimmte Partikel |
WO2001045676A2 (fr) | 1999-12-20 | 2001-06-28 | Schering Corporation | Composition de dose orale a liberation prolongee |
WO2001045668A2 (fr) * | 1999-12-20 | 2001-06-28 | Schering Corporation | Composition de dose orale a liberation prolongee |
US7135465B2 (en) * | 2000-03-30 | 2006-11-14 | Bristol-Myers Squibb Company | Sustained release beadlets containing stavudine |
CN1329482C (zh) * | 2002-06-24 | 2007-08-01 | 株式会社艾迪科 | 阻燃剂组合物以及含有该组合物的阻燃性树脂组合物 |
AU2003291457A1 (en) * | 2002-11-08 | 2004-06-03 | Glaxo Group Limited | Pharmaceutical antiviral compositions |
BRPI0415322A (pt) * | 2003-10-01 | 2006-12-05 | Lupin Ltd | composição farmacêutica antiretroviral, processo para a preparação de uma composição farmacêutica antiretroviral, método para reduzir a carga de consumo de pìlulas para um paciente, método para aumentar a meia-vida in vivo de lamivudina e de zidovudina enquanto não afetando a meia-vida de nevirapina |
GB0403247D0 (en) | 2004-02-13 | 2004-03-17 | Tillotts Pharma Ag | A pharmaceutical composition |
US7611630B2 (en) * | 2004-03-30 | 2009-11-03 | Bend Research, Inc. | Method and device for evaluation of pharmaceutical compositions |
US20100062073A1 (en) * | 2006-11-29 | 2010-03-11 | Ronald Arthur Beyerinck | Pharmaceutical compositions comprising nanoparticles comprising enteric polymers casein |
US20100119612A1 (en) * | 2007-04-17 | 2010-05-13 | Bend Research, Inc | Nanoparticles comprising non-crystalline drug |
US20100080852A1 (en) * | 2007-05-03 | 2010-04-01 | Ronald Arthur Beyerinck | Phamaceutical composition comprising nanoparticles and casein |
US8309129B2 (en) * | 2007-05-03 | 2012-11-13 | Bend Research, Inc. | Nanoparticles comprising a drug, ethylcellulose, and a bile salt |
WO2008135855A2 (fr) * | 2007-05-03 | 2008-11-13 | Pfizer Products Inc. | Nanoparticules contenant un inhibiteur de la protéine de transfert d'ester de cholestéryle et un polymère non ionisable |
US8974827B2 (en) * | 2007-06-04 | 2015-03-10 | Bend Research, Inc. | Nanoparticles comprising a non-ionizable cellulosic polymer and an amphiphilic non-ionizable block copolymer |
WO2008149230A2 (fr) | 2007-06-04 | 2008-12-11 | Pfizer Products Inc. | Nanoparticules comprenant un médicament, un polymère cellulosique non ionisable et du tocophéryl polyéthylène glycol succinate |
EP2178518A2 (fr) * | 2007-07-13 | 2010-04-28 | Bend Research, Inc | Nanoparticules comprenant des polymères cellulosiques ionisables faiblement solubles dans l'eau |
US9724362B2 (en) * | 2007-12-06 | 2017-08-08 | Bend Research, Inc. | Pharmaceutical compositions comprising nanoparticles and a resuspending material |
US9233078B2 (en) * | 2007-12-06 | 2016-01-12 | Bend Research, Inc. | Nanoparticles comprising a non-ionizable polymer and an Amine-functionalized methacrylate copolymer |
US20140271893A1 (en) * | 2013-03-15 | 2014-09-18 | Mcneil-Ppc, Inc. | Coated phenylephrine particles and use thereof in pharmaceutical formulations |
CN106333957A (zh) * | 2016-08-19 | 2017-01-18 | 丁静 | 齐多夫定用于制备自身免疫性神经炎治疗药物的应用 |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
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GB2209669A (en) * | 1987-09-11 | 1989-05-24 | Squibb & Sons Inc | Pharmaceutical composition containing high drug load |
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BE785702A (fr) * | 1971-07-14 | 1972-10-16 | Roehm Gmbh | Produits de revetement de formes medicamenteuses et leur utilisation |
BE787973A (fr) * | 1971-09-04 | 1973-02-26 | Beecham Group Ltd | Comprimes pharmaceutiques a effet retard |
ES438635A1 (es) * | 1974-06-24 | 1977-02-16 | Shinetsu Chemical Co | Procedimiento para el revestimiento de moldes solidos de do-sificacion. |
EP0052075A1 (fr) * | 1980-11-12 | 1982-05-19 | Ciba-Geigy Ag | Granule pharmaceutique à action retardée |
ATE13486T1 (de) * | 1980-11-12 | 1985-06-15 | Ciba Geigy Ag | Schnellzerfallende arzneimittel-presslinge. |
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JPS59193831A (ja) * | 1983-04-18 | 1984-11-02 | Sankyo Co Ltd | 腸溶性製剤の製造法 |
JPS59227817A (ja) * | 1983-06-07 | 1984-12-21 | Toyo Jozo Co Ltd | 持続性経口用ブレデニン製剤 |
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AU572019B2 (en) * | 1985-03-16 | 1988-04-28 | Wellcome Foundation Limited, The | 3'-azido-3'-deoxythymidine |
DK166805B1 (da) * | 1985-03-16 | 1993-07-19 | Wellcome Found | Threo-isomeren af 3'-azido-3'-deoxythymidin til anvendelse ved behandling af eller profylakse for humane retrovirusinfektioner, anvendelse af forbindelsen til fremstilling af et laegemiddel med naevnte indikation og farmaceutisk praeparat indeholdende forbindelsen |
GB8506869D0 (en) * | 1985-03-16 | 1985-04-17 | Wellcome Found | Antiviral compound |
US4724232A (en) * | 1985-03-16 | 1988-02-09 | Burroughs Wellcome Co. | Treatment of human viral infections |
GB8519310D0 (en) * | 1985-07-31 | 1985-09-04 | Zyma Sa | Granular active substances |
-
1987
- 1987-03-27 GB GB878707421A patent/GB8707421D0/en active Pending
-
1988
- 1988-03-25 EP EP88302657A patent/EP0284407B1/fr not_active Expired - Lifetime
- 1988-03-25 IE IE89988A patent/IE60605B1/en not_active IP Right Cessation
- 1988-03-25 AT AT88302657T patent/ATE63818T1/de not_active IP Right Cessation
- 1988-03-25 JP JP63071708A patent/JP2719344B2/ja not_active Expired - Lifetime
- 1988-03-25 CA CA000562420A patent/CA1308026C/fr not_active Expired - Lifetime
- 1988-03-25 DE DE8888302657T patent/DE3862974D1/de not_active Expired - Lifetime
- 1988-03-25 DK DK198801643A patent/DK175348B1/da not_active IP Right Cessation
- 1988-03-25 ES ES198888302657T patent/ES2033426T3/es not_active Expired - Lifetime
- 1988-03-25 IL IL85870A patent/IL85870A/xx not_active IP Right Cessation
- 1988-03-25 US US07/173,261 patent/US4917900A/en not_active Expired - Lifetime
- 1988-03-25 PT PT87081A patent/PT87081B/pt not_active IP Right Cessation
- 1988-03-25 AU AU13756/88A patent/AU607474B2/en not_active Expired
- 1988-03-25 ZA ZA882168A patent/ZA882168B/xx unknown
- 1988-03-25 KR KR1019880003222A patent/KR960013434B1/ko not_active IP Right Cessation
- 1988-03-25 NZ NZ224026A patent/NZ224026A/xx unknown
-
1991
- 1991-05-30 GR GR91400615T patent/GR3002030T3/el unknown
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB2209669A (en) * | 1987-09-11 | 1989-05-24 | Squibb & Sons Inc | Pharmaceutical composition containing high drug load |
Also Published As
Publication number | Publication date |
---|---|
DK164388A (da) | 1988-09-28 |
JPS63255230A (ja) | 1988-10-21 |
EP0284407A2 (fr) | 1988-09-28 |
IE60605B1 (en) | 1994-07-27 |
KR960013434B1 (ko) | 1996-10-05 |
JP2719344B2 (ja) | 1998-02-25 |
GR3002030T3 (en) | 1992-12-30 |
AU1375688A (en) | 1988-09-29 |
KR880010759A (ko) | 1988-10-24 |
NZ224026A (en) | 1991-03-26 |
PT87081A (pt) | 1988-04-01 |
ATE63818T1 (de) | 1991-06-15 |
IE880899L (en) | 1988-09-27 |
GB8707421D0 (en) | 1987-04-29 |
US4917900A (en) | 1990-04-17 |
AU607474B2 (en) | 1991-03-07 |
DE3862974D1 (de) | 1991-07-04 |
IL85870A (en) | 1992-02-16 |
DK175348B1 (da) | 2004-09-06 |
PT87081B (pt) | 1992-07-31 |
DK164388D0 (da) | 1988-03-25 |
ZA882168B (en) | 1989-11-29 |
CA1308026C (fr) | 1992-09-29 |
EP0284407A3 (en) | 1988-12-14 |
ES2033426T3 (es) | 1993-03-16 |
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